Neratinib is a kinase inhibitor indicated for the extended adjuvant treatment of adult patients with early stage HER2-overexpressed/amplified breast cancer, to follow adjuvant trastuzumab-based therapy.
Neratinib is a kinase inhibitor that irreversibly binds to Epidermal Growth Factor Receptor (EGFR), Human Epidermal Growth Factor Receptor 2 (HER2), and HER4. In vitro, neratinib reduces EGFR and HER2 autophosphorylation, downstream MAPK and AKT signaling pathways, and showed antitumor activity in EGFR and/or HER2 expressing carcinoma cell lines. Neratinib human metabolites M3, M6, M7 and M11 inhibited the activity of EGFR, HER2 and HER4 in vitro. In vivo, oral administration of neratinib inhibited tumor growth in mouse xenograft models with tumor cell lines expressing HER2 and EGFR.
Dosage & Administration
Antidiarrheal prophylaxis: Initiate loperamide with the first dose of Neratinib and continue during first 2 cycles (56 days) of treatment. Instruct patients to maintain 1-2 bowel movements per day and on how to use antidiarrheal treatment regimens
Recommended dose: 240 mg (6 tablets) given orally once daily with food, continuously for one year. Dose interruptions and/or dose reductions are recommended based on individual safety and tolerability
Hepatic Impairment: Reduce starting dose to 80 mg in patients with severe hepatic impairment.
Gastric acid reducing agents: Avoid concomitant use with proton pump inhibitors (PPI) and H2-receptor antagonists. Separate Neratinib by 3 hours after antacid dosing.
Strong or moderate CYP3A4 inhibitors: Avoid concomitant use.
Strong or moderate CYP3A4 inducers: Avoid concomitant use.
P-glycoprotein (P-gp) substrates: Monitor for adverse reactions of narrow therapeutic agents that are P-gp substrates when used concomitantly with Neratinib.
The most common adverse reactions (> 5%) were diarrhea, nausea, abdominal pain, fatigue, vomiting, rash, stomatitis, decreased appetite, muscle spasms, dyspepsia, AST or ALT increase, nail disorder, dry skin, abdominal distention, weight decreased and urinary tract infection.
Pregnancy & Lactation
There are no available data in pregnant women to inform the drug-associated risk. No data are available regarding the presence of neratinib or its metabolites in human milk or its
effects on the breastfed infant or on milk production.
Precautions & Warnings
Diarrhea: Aggressively manage diarrhea occurring despite recommended prophylaxis with additional antidiarrheals, fluids, and electrolytes as clinically indicated. Withhold Meratinib in patients experiencing severe and/or persistent diarrhea. Permanently discontinue Meratinib in patients experiencing Grade 4 diarrhea or Grade ≥ 2 diarrhea that occurs after maximal dose reduction.
Hepatotoxicity: Monitor liver function tests monthly for the first 3 months of treatment, then every 3 months while on treatment and as clinically indicated. Withhold Meratinib in patients experiencing Grade 3 liver abnormalities and permanently discontinue Meratinib in patients experiencing Grade 4 liver abnormalities.
Embryo-Fetal Toxicity: Meratinib can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception.
Use in Special Populations
Pediatric Use: The safety and efficacy of Neratinib in pediatric patients has not been established.
There is no specific antidote, and the benefit of hemodialysis in the treatment of Neratinib overdose is unknown. In the event of an overdose, administration should be withheld and general supportive measures undertaken. In the clinical trial setting, a limited number of patients reported overdose. The adverse reactions experienced by these patients were diarrhea, nausea, vomiting, and dehydration. The frequency and severity of gastrointestinal disorders (diarrhea, abdominal pain, nausea and vomiting) appear to be dose related.
Tyrosine Kinase Inhibitor
Store Neratinib at room temperature between 20° to 25°C. Keep Neratinib and all medicines out of the reach of children.
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